ABSTRACT: Project 3, Multi-omic analysis to expand phenotype in MMRRC mice Established by the NIH 20 years ago, the MMRRC serves the biomedical research community by preserving, protecting, and promoting the considerable national investment in creating and phenotyping mutant mouse models for the study of human biology and disease. With a census today exceeding 60,000 alleles, the MMRRC ensures that unique and scientifically valuable mouse strains produced and studied in independent PI laboratories can be deposited and archived for safekeeping so that they are available and accessible in perpetuity for scientists to obtain and use for their research studies. But the phenotypic description of mutant mice submitted to the MMRRC often narrowly reflects the specific scientific interests of the submitting investigator, reflecting the focus of the researcher who developed the line. Therefore, the phenotypic repertoire of many (if not most) MMRRC lines is far more diverse than what is known. For that reason, anything the MMRRC can do to expose these hidden phenotypes will at least add new knowledge about a line, some (if not most) of which will be scientifically valuable. Therefore, this project will pilot the feasibility of conducting relatively high-throughput, low cost, and unbiased phenotyping analyses to each mouse line submitted to the MMRRC. To that end, we propose to use extant, in-house transcriptomic, proteomic, and metabolomic platforms to establish a reliable and cost-effective protocol for high-fidelity multi-omic analysis of mouse tissues from MMRRC mice. We will conduct this study in two aims over the course of 5 years. The first aim will establish and test procedures in wildtype mice, and in the second aim apply the protocol to reveal new phenotypes in MMRRC strains. We expect that comprehensive multi-omic characterization of submitted mouse lines will not only contribute to validating what is already known (i.e., reproducibility and reliability) but also will add an abundance of new phenotypic knowledge about MMRRC mouse lines. With this additional molecular information, the research utility of mutant mouse lines held by the MMRRC Consortium will increase, resulting in a growth in requests and greater use by the research community, and enhancing the distribution activity of the resource.